Global Prevalence and Specificity of Red Blood Cell Antibodies in Blood Donors: A Systematic Review and Meta-Analysis

Background: Red blood cell (RBC) antibody screening in blood donors is a key component of transfusion safety. However, reported prevalence and antibody specificities vary widely across studies, and a consolidated global estimate remains limited. This study aimed to quantify the prevalence of RBC antibody detection among blood donors, identify factors associated with variation in reported prevalence, and summarize antibody specificities. Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed, MEDLINE, Embase, Scopus, and Google Scholar were searched from inception to 27 August 2025 for observational studies reporting RBC antibody detection in blood donors. Methodological quality was assessed using the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data. Pooled prevalence estimates were synthesized using random-effects models. Subgroup analyses, meta-regression, leave-one-out sensitivity analyses, and publication-bias assessments were performed. Associations between ABO blood group and RBC antibody detection were summarized using pooled odds ratios. The review protocol was registered in PROSPERO (CRD420251181987). Results: Forty-one studies comprising 43 reports and 3,561,088 blood donors from 18 countries were included. The pooled prevalence of RBC antibody detection was 0.2% (95% CI: 0.2-0.3%), with substantial between-study heterogeneity (I²: 99.61%) and a 95% prediction interval of 0.0-1.4%. Prevalence was higher in female donors than in male donors (0.5% vs. 0.1%). Publication year was inversely associated with reported prevalence, although temporal and methodological effects could not be separated. An exploratory analysis based on six studies showed higher estimated odds of antibody detection among blood group AB donors (OR: 1.20, 95% CI: 1.07-1.34). Among clinically significant antibodies, Rh and Kell specificities were predominated. Anti-Mi^a was prominent in Southeast Asian populations. Conclusions: RBC antibody detection among blood donors was uncommon overall but varied considerably across settings. Interpretation is limited by substantial methodological heterogeneity, uneven geographic representation, and incomplete reporting of donor characteristics. The pooled estimate should be interpreted as an international benchmark rather than a uniform prevalence applicable to individual blood services. This large-scale synthesis may inform context-specific donor antibody screening, confirmatory testing, component management, and hemovigilance policies.